Clinical pharmacology of cannabinoids in early phase drug development

Abstract

Although cannabis is especially known for its recreational use as a __soft drug__, its potential therapeutic properties have been recognized for hundreds of years. Since the isolation of THC from Cannabis sativa L, the discovery of cannabinoid receptors and their natural ligands (endocannabinoids) the interest in the development of novel cannabinoids as medicine is accelerating. This thesis describes useful cannabis-biomarkers and the clinical pharmacology of some cannabinoid agonists and antagonists in early phase drug development. This includes a novel mode of pure intrapulmonary THC administration that can be used as a benchmark for novel CB1/CB2-agonists, or to demonstrate inhibitory activity of CB1-antagonists. In addition, the pharmacodynamics and pharmacokinetics of two novel CB1/CB2 agonists are evaluated and compared with the pharmacodynamic effect profile of THC. The clinical trials carried out for this research were performed at the Centre for Human Drug Research, Leiden, The Netherlands.